Description of Research Expertise

Description of Research
The patterning and formation of the skeleton lends form and function to all vertebrate organisms; the maintenance and remodeling of bone in the adult is a striking example of tissue homeostasis via stem cells. We are taking genetic and cellular approaches in the zebrafish to understand both the early events in skeletal development and the regeneration of bone in the adult after injury. We have developed lines of transgenic zebrafish expressing fluorescent proteins in bone and cartilage, allowing us to visualize the establishment of the skeleton in live fish. We have also developed a method to trace cell lineages in the zebrafish, and used it to establish the contribution of neural crest to the skeleton.

A second area of focus is in comparative genomics, examining how the sequences regulating transcription of important skeletal genes have evolved and function in diverse organisms. We have developed a highly efficient approach using zebrafish transgenesis to identify and study regulatory sequences, from the genomes of zebrafish and of distantly related species like human and mouse. We are applying this approach on a large scale to identify enhancers that control expression in skeletal tissues. These regulatory elements provide insight into the signaling pathways that control bone and cartilage formation, and variants in their sequence and function are likely to contribute to human diseases affecting the skeleton.

Rotation projects
Identify the regulatory elements for a gene important in skeletal development or associated with a human genetic disease, using zebrafish transgenesis
Describe an aspect of bone and cartilage formation using time-lapse microscopy, in wild-type or mutant zebrafish
Build and test constructs to aid in development of new technologies to manipulate the zebrafish genome